Metacyclic promastigotes are highly virulent to a susceptible vertebrate host. This virulence appears to be related to the ability of metacyclic forms to resist killing by the alternative complement pathway, and to their ability to resist the microbicidal activities of normal resident macrophages. A monoclonal antibody has been raised which recognizes a cell surface and secreted molecule which is unique to metacyclic promastigotes. It appears to be the exclusive molecule actively secreted by infective stage organisms. It is, therefore, likely to play a biologically critical role in promoting successful parasitism. Its chemistry and mode of action are being pursued. Approximately 2 months of each year are spent studying the immunology of visceral leishmaniasis in north India. Patients with active disease are specifically unresponsive at the T cell level to leishmanial antigens. This unresponsiveness cannot be reversed by depletion of T8 "suppressor" cells or by reconstitution with IL-2. We have recently detected a potentially large population of exposed, asymptomatic individuals from endemic areas based on their reactivity to parasite antigens in vivo and in vitro. The nature of the antigens recognized by the "immune" T cells is under study.